Development of a childhood metabolic syndrome risk score for predicting adult disease. Project summary: The metabolic syndrome describes a group of medical findings that appear to be linked by an underlying process that increases risk for diabetes and heart disease. The best way to diagnose the metabolic syndrome in children remains unclear, though current attempts appear to result in racial/ethnic discrepancies. We propose to formulate a new race/ethnicity-specific MetS risk score for children by using known markers of disease risk as well as long-term information on the development of diabetes and heart disease. Children identified as having increased risk of adult disease could be targeted to receive increased efforts at prevention. PUBLIC HEALTH RELEVANCE: Development of a childhood metabolic syndrome risk score for predicting adult disease. Narrative: The metabolic syndrome (MetS) is a cluster of cardiovascular indices that appear to be linked by a poorly-understood insidious process that increases risk for Type 2 diabetes (T2DM) and coronary artery disease (CAD). These components of MetS include abdominal obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, and insulin resistance. The diagnosis of MetS is currently based on a combination of cut-off points for these different components. For children, there is not a consensus regarding which of several sets of pediatric MetS criteria to use clinically. Much of this uncertainty is related to the difficulty in linking long-term outcomes to a diagnosis of MetS, since children take a longer period of time to develop T2DM and CAD. Additionally, MetS criteria in adults have been shown to exhibit racial/ethnic discrepancies in their ability to predict T2DM and CAD. We propose to design a race/ethnicity-specific MetS risk score for children, using other serum factors known to be associated with long-term risk for adult coronary artery disease. These "surrogate" risk factors include fasting insulin, C-reactive protein, uric acid, and alanine aminotransferase. We will then validate and determine risk thresholds for this risk score, using longitudinal data that includes MetS information during childhood and adult outcomes data. Our plan is three-fold. We will first use the National Health and Nutrition Examination Survey (NHANES) to test current pediatric MetS criteria, with a hypothesis that we will demonstrate racial/ethnic discrepancies in the ability of current MetS criteria to predict elevations in our surrogates for adult disease. We will then use NHANES to design a race/ethnicity-specific pediatric MetS risk score, using elevations in our surrogates as a "target" and using linear regression to formulate this risk score using measurements of the components of MetS. Finally, we will validate this risk score and set thresholds that best predict long-term outcomes using the Lipid Research Clinic/Princeton Follow-up Study, with data from both childhood measurements of MetS and adult disease outcomes, which will be updated as part of this proposal. We will also validate our score using additional databases, including updated NHANES data and data from a pediatric obesity clinic at UVa. We expect to use this experimental design to produce a clinically accessible and interpretable MetS risk score that can be used to identify children at higher risk for developing adult diseases related to MetS, who could then be targeted for increased intervention.